title: Interactions in the renal and biliary elimination of digoxin: stereoselective difference between quinine and quinidine.
abstract: The interactions between digoxin and quinine and quinidine that affect the renal and biliary clearances of digoxin were investigated in eight healthy subjects. Digoxin (0.5 to 0.75 mg/day) was given alone and with concomitant administration of quinine (750 mg/day) to reach a steady-state level. In four of the subjects, the study was repeated by administration of equimolar doses of the diastereoisomer quinidine together with digoxin, enabling a within-subject comparison of the effects of the two isomers on digoxin clearance. The biliary excretion of digoxin was studied by use of a modified duodenal marker perfusion technique. A marked reduction was found in the steady-state biliary clearance of digoxin from control value 134 +/- 57 ml/min (mean +/- SD) to 87 +/- 39 ml/min during treatment with quinine (p less than 0.05) and from 95 +/- 24 to 55 +/- 27 ml/min during treatment with quinidine (p less than 0.01; n = 4). Quinidine reduced the renal clearance of digoxin (155 +/- 26 versus 110 +/- 21 ml/min) (p less than 0.05; n = 4), whereas quinine had no such effect (177 +/- 40 versus 185 +/- 53 ml/min; not significant). These findings explain the difference in magnitude between quinidine and quinine in regard to the interaction with digoxin and imply a different degree of stereoselectivity for these isomers in the renal and biliary secretory systems of digoxin.
authors.affiliation: Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Hedman
authors.forename: B
authors.initials: B
authors.lastname: Angelin
authors.forename: A
authors.initials: A
authors.lastname: Arvidsson
authors.forename: R
authors.initials: R
authors.lastname: Dahlqvist
authors.forename: B
authors.initials: B
authors.lastname: Nilsson
mesh_terms: D000328:Adult; D001646:Bile / Q000378:metabolism*; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics*; D004386:Duodenum; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D010477:Perfusion; D011802:Quinidine / Q000097:blood / Q000494:pharmacology*; D011803:Quinine / Q000097:blood / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D004077:Digoxin; D011803:Quinine; D011802:Quinidine